This invention relates to a procedure, and a product obtained from that procedure, for increasing the clot activation properties of serum separation tubes once a blood sample has been introduced into the tube. More particularly, this invention relates to a product easily produced separately from such a blood sample collection tube, and which may be easily introduced in a mass production line into a plurality of such tubes, and which product has the effect of increasing the degree of clot activation of the blood sample introduced, as well as reducing the clotting time thereof. More particularly, this invention relates to the development of a particular kind of glass particle or piece from a sol-gel process, which particles or pieces of glass are extremely porous, having a sponge-like rigid amorphous body. The pieces of glass, because of the porous property thereof, fragments upon contact with a blood sample introduced into a serum separation tube containing such particles or pieces, because the blood, by capillary action, enters the interstices of the pieces or particles and causes them to fragment. This fragmentation causes sound and shock waves throughout the blood sample. The sound and shock waves increase the degree of clotting and decrease, simultaneously, the clotting time of the sample.
The length of time required for blood collected in a blood collection assembly to clot after it is introduced into the assembly is dependent upon a number of interrelated factors. One of the factors which increases the rate of clot formation is exposure of the blood to "siliceous" materials such as glass, silica, kaolin, bentonite or diatomaceous earth. Therefore, it is important that the exposure of the blood sample to the presence of a silica in a sample containing tube be as uniform and rapid as possible.
Representative prior art patents which teach, among other things, silica coatings in blood collection tubes, such as serum separation tubes, include U.S. Pat. Nos. 4,153,739 and 4,257,886. The '739 patent teaches a clot activating film 24 with the film being formed of one percent by weight polyvinyl pyrrolidone and one percent by weight silica added to isopropanol. In substitution for polyvinyl pyrrolidone, polyethylene oxide may be used. The '886 patent teaches, on the other hand, a water-soluble clot activating coating 36 wherein the coating is comprised of an admixture of polyvinyl pyrrolidone or polyethylene oxide with clot activating particles such as silica in a solvent such as isopropanol. In both cases the source of the silica is fine silica particles. A further teaching of coatings which provide an enhancement of clot activation is in co-pending U.S. application Ser. No. 375,635 filed May 6, 1982.
While the methods taught in the two patents noted above, as well as the co-pending application, have proved satisfactory in the sense that they produce coatings on substrates such as serum separation tubes, which coatings contain silica for clot activation, all of these approaches require adherance to certain rigid production techniques in order to provide proper coating on the inside of relatively small blood collection tubes. These coatings must be uniform and contain the proper ratio of the individual components in the coatings in order to provide the proper and accurate test results, subsequently, in a clinical laboratory testing the blood specimen contained in the containers.
With this invention, by contrast, an extremely simple approach is provided in the sense that the blood clot activator for such blood collection sample tubes may be produced separately in a simple sol-gel process. No coating procedures are required. A particular kind of glass piece or particle is produced by the sol-gel process of this invention which pieces and/or particles may be introduced in a production line procedure by being simply dropped into the individual tubes, rather than going through a coating procedure. The pieces are, for want of a better word, comprised of an imperfect glass. That is, the pieces are comprised of an amorphous porous glass much in the same form as a sponge, although being relatively rigid. Thus, when blood is introduced into a blood collection tube containing the amorphous glass pieces or particles of the invention, the blood passes into the interstices or pores of the glass of the invention and shatters it. This shattering causes shock waves and sound, both of which properties act to increase the rapidity of clot activation in the blood sample, as well as increasing the degree of clot activation.
In considering generally the conditions for carrying out the process of this invention, ethylsilicate is dissolved in ethyl alcohol in a ratio of 1:1 by volume and hydrolyzed by the addition of an acid or a base such as ammonia, acetic acid, sulphuric acid or hydrochloric acid. Preferably, 1-2% 6N hydrochloric acid is added in the presence of less than a stoichiometric amount of water according to the reaction; ##STR1## The ethylsilicate is partially hydrolyzed and is, thereafter, polymerized at room temperature to form a gel, according to the following reaction; ##STR2## This gel is the resulting silica glass in a semi-solid form. The semi-solid form is simply allowed to dry at room temperature thereafter for two to three hours, followed by heating at a relatively low temperature to drive off the ethyl alcohol, the water and excess hydrochloric acid, leaving the small pores originally formed in the formed glass contained in the glass. It is, in effect, an unfinished amorphous-like or rigid sponge-like inorganic material in the form of relatively large pieces or particles of the material, which may then be introduced into the blood collection tubes.
With the foregoing and additional objects in view, this invention will now be described in more detail, and other objects and advantages thereof will be apparent from the following description, the accompanying drawing, and the appended claims.